It Seems the Fertility Clock Ticks for Men, Too

By RONI RABIN

Published: February 27, 2007

When it comes to fertility and the prospect of having normal babies, it has always been assumed that men have no biological clock -- that unlike women, they can have it all, at any age.

But mounting evidence is raising questions about that assumption, suggesting that as men get older, they face an increased risk of fathering children with abnormalities. Several recent studies are starting to persuade many doctors that men should not be too cavalier about postponing marriage and children.

Until now, the problems known to occur more often with advanced paternal age were so rare they received scant public attention. The newer studies were alarming because they found higher rates of more common conditions -- including autism and schizophrenia -- in offspring born to men in their middle and late 40s. A number of studies also suggest that male fertility may diminish with age.

''Obviously there is a difference between men and women; women simply can't have children after a certain age,'' said Dr. Harry Fisch, director of the Male Reproductive Center at New York-Presbyterian Hospital/Columbia University Medical Center and the author of ''The Male Biological Clock.''

''But not every man can be guaranteed that everything's going to be fine,'' Dr. Fisch said. ''Fertility will drop for some men, others will maintain their fertility but not to the same degree, and there is an increased risk of genetic abnormalities.''

It's a touchy subject. ''Advanced maternal age'' is formally defined: women who are 35 or older when they deliver their baby may have ''A.M.A.'' stamped on their medical files to call attention to the higher risks they face. But the concept of ''advanced paternal age'' is murky. Many experts are skeptical about the latest findings, and doctors appear to be in no rush to set age guidelines or safety perimeters for would-be fathers, content instead to issue vague sooner-rather-than-later warnings.

''The problem is that the data is very sparse right now,'' said Dr. Larry Lipschultz, a specialist in the field of male infertility and a past president of the American Society for Reproductive Medicine. ''I don't think there's a consensus of what patients should be warned about.''

And many men maintain their fertility, said Dr. Rebecca Z. Sokol, president of the Society of Male Reproduction and Urology.

''If you look at males over 50 or 40, yes, there is a decline in the number of sperm being produced, and there may be a decline in the amount of testosterone,'' Dr. Sokol said. But by and large, she added, ''the sperm can still do their job.''

Some advocates, however, welcome the attention being paid to the issue of male fertility, saying it is long overdue and adding that it could level the playing field between men and women in the premarital dating game.

''The message to men is: 'Wake up and smell the java,' '' said Pamela Madsen, executive director of the American Fertility Association, a national education and advocacy group. '' 'It's not just about women anymore, it's about you too.' ''

''It takes two to make a baby,'' she said, ''and men who one day want to become fathers need to wake up, read what's out there and take responsibility.

''I don't see why everyone is so surprised,'' Ms. Madsen added. ''Everyone ages. Why would sperm cells be the only cells not to age as men get older?''

Analyses of sperm samples from healthy men have found changes as men age, including increased fragmentation of DNA, and some studies outside the United States have noted increased rates of some cancers in children of older fathers.

Geneticists have been aware for decades that the risk of certain rare birth defects increases with the father's age. One of the most studied of these conditions is a form of dwarfism called achondroplasia, but the list also includes neurofibromatosis, the connective-tissues disorder Marfan syndrome, skull and facial abnormalities like Apert syndrome, and many other diseases and abnormalities.

''We have counseled for quite a long time that as paternal age increases, there is an increased frequency in new mutations,'' said Dr. Joe Leigh Simpson, president-elect of the American College of Medical Genetics.

Some studies suggest that the risk of sporadic single-gene mutations may be four to five times higher for fathers who are 45 and older, compared with fathers in their 20s, Dr. Simpson said. Over all, having an older father is estimated to increase the risk of a birth defect by 1 percent, against a background 3 percent risk for a birth defect, he said.

Even grandchildren may be at greater risk for some conditions that are not expressed in the daughter of an older father, according to the American College of Medical Genetics. These include Duchenne muscular dystrophy, some types of hemophilia and fragile-X syndrome.

A recent study on autism attracted attention because of its striking findings about a perplexing disorder. Researchers analyzed a large Israeli military database to determine whether there was a correlation between paternal age and the incidence of autism and related disorders. It found that children of men who became a father at 40 or older were 5.75 times as likely to have an autism disorder as those whose fathers were younger than 30.